The Targeted Genomics Facilities Core (TGFC) is part of an integrated Facility Core program consisting of hypothesis generating, testing, and translational resources within an Integrated Discovery Pipeline, designed to accelerate and advance innovative ideas from hypothesis to practice. The goal of the TGFC is to provide CTEHR investigators with access to highly sophisticated and tailored genetically engineered mouse and modified human cell model systems, which can be used to test novel hypothesis generated by Center members doing cutting-edge EHS research. In the last few years there have been important advances in the gene targeting approaches for generating genetically engineered cells and transgenic animals, including gene trap, engineered nuclease (ZFN) and TALEN technologies. The TGFC will provide CTEHR investigators with streamlined and cost effective generation of genetically engineered (and validated) model systems for their research. The TGFC has both the technology and the necessary expertise to develop these models for investigators in all the of the CTEHR Thematic Focus Areas, by applying economies of scale to their production and validation, and by leveraging the resources already available within the participating institutions. The TGFC will facilitate timely research advances through the following Specific Aims: Aim 1. Maintain the skilled personnel, molecular technologies and research infrastructure necessary for the generation of state-of-the-art genetically engineered model systems to support CTEHR research. Aim 2. Provide members with cost effective, prioritized access to services that support the development and use of genetically engineered model systems (cell lines and transgenic mice) to study interactions between the genome and environmental factors that impact human health and disease. Aim 3. Educate CTEHR members about the application of state-of-the-art genetic engineering technologies to research on the effects of environmental factors on human health and support the career development and mentoring activities of Center investigators Aim 4. Facilitate the translational research activities on the interactions between the genome and environmental factors that impact human health through interactions with the other CTEHR Facility Cores and Programs. The TGFC will provide access to powerful research technologies that will enable CTEHR members to develop and test innovative hypotheses focusing on genome - environment interactions, and their effect on human health. This Core provides the opportunity to evaluate and validate new concepts in genetically relevant model systems as part of integrated discovery pipeline involving hypothesis generation, testing and translation. Use of this pipeline will accelerate the process of advancing innovative ideas and translating them to improvement of environmental health and mitigation of environmental disease.